Natriuretic peptide receptor-B (NPRB, GC-B) (NPRB)

Natriuretic peptide receptor-B (NPRB), also known as guanylyl cyclase B (GC-B), is a transmembrane receptor that is primarily activated by C-type natriuretic peptide (CNP)[1][4]. It is a member of the natriuretic peptide receptor family, which includes NPR-A (GC-A) and NPR-C (clearance receptor). NPRB is distinct in its tissue distribution and physiological roles, being especially important in bone growth, cartilage development, and vascular homeostasis[1][4]. Structurally, it contains a large extracellular ligand-binding domain, a single transmembrane region, and an intracellular guanylyl cyclase domain that generates cGMP upon activation[1][4]. NPRB is overexpressed in certain tumor microenvironments, where its activation can normalize dysfunctional tumor vasculature, improve blood perfusion, and reduce metastasis in preclinical models[4]. Human mutations in NPRB are associated with skeletal growth disorders, underscoring its critical role in bone biology[1]. While no drugs specifically targeting NPRB are currently approved, novel CNP analogs (e.g., dCNP) are being explored for their potential to remodel tumor vasculature and treat certain types of cancer[4]. The receptor's role in cardiovascular and metabolic regulation is an area of ongoing research, but it remains less well-characterized than NPR-A in the context of heart disease[1][2]. NPRB represents a promising but still emerging therapeutic target, particularly in growth disorders and cancer angiogenesis[4].

Other names

Guanylyl cyclase BGC-BNPR2NPRB receptor

Activation by C-type natriuretic peptide (CNP) Catalyzes synthesis of intracellular cyclic GMP (cGMP) upon ligand binding cGMP activates protein kinase G (PKG), phosphodiesterases, and ion channels Downstream effects include vascular endothelial stabilization, pericyte recruitment, reduced vascular leakage, and modulation of cell proliferation and inflammation[1][4]